SpeakingX

Drupal customization is an art and life-time commitment.
File permissions
In general you don't need to change any permissions after you extract all the Drupal files. The only thing you need to pay close attention is the infamous "files" directory. I created this directory in sites/default/ instead of directly under drupal's root directory, which will make Drupal upgrade a bit easier. So how to set the right permission of this folder? I'll show you what I did below, which basically a re-post of an article I wrote before.
First of all, I would not set it to "777" as suggested by some people. This makes the directory world writable. The fact is we only need to give the write permission to the web server. Assuming you are installing drupal locally and create "files" folder as "root" , first add group writing permission first by:

chmod g+w files

Then associate "files" folder to web server's group, which usually is "apache" if apache web server is used.

chgrp apache files

You can find out apache's user id and group name by check your server setting or user and group list. All the user and group names are in etc/passwd and etc/group, respectively (redhat/fedora/CentOS).

Basic site configurations

• Administer › Site configuration
• clean url (see handbook for enabling the module in apache)
• date and time
• error reporting
• don't forget to setup cron, which is needed for search and clearing log files and cache.

...

Contributed modules
This is the part on which you will probably spend most of your time. Drupal.org has a huge selection of modules. Picking a right module for your task can be very challenging.
First create sites/all/modules folder which will be the home to all the contributed modules. Separating contributed modules from Drupal core modules is highly recommended as it will make your life as an website administrator much easier, such as upgrading drupal. Also in so doing you could enjoy the best out of Drupal's powerful multi-site feature.

Contributed themes and theme customization
Again, we create the sites/all/themes sub-folder

More to come ...